Tau – an inhibitor of deacetylase HDAC6 function

Authors

  • Mar Perez,

    1. Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Universidad Autonoma de Madrid, Madrid, Spain
    2. Facultad de Medicina, Universidad Autonoma de Madrid (UAM), Madrid, Spain
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    • These two authors contributed equally to this work.

  • Ismael Santa-Maria,

    1. Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Universidad Autonoma de Madrid, Madrid, Spain
    2. CIBERNED, Madrid, Spain
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    • These two authors contributed equally to this work.

  • Elena Gomez De Barreda,

    1. Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Universidad Autonoma de Madrid, Madrid, Spain
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  • Xiongwei Zhu,

    1. Department of pathology, Case Western Reserve University, Cleveland, Ohio, USA
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  • Raquel Cuadros,

    1. Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Universidad Autonoma de Madrid, Madrid, Spain
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  • Jose Roman Cabrero,

    1. Departamento de Biología Vascular e Inflamación, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain
    2. Servicio de Inmunologia, Hospital de la Princesa, Universidad Autonoma de Madrid, 28006 Madrid, Spain
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  • Francisco Sanchez-Madrid,

    1. Departamento de Biología Vascular e Inflamación, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain
    2. Servicio de Inmunologia, Hospital de la Princesa, Universidad Autonoma de Madrid, 28006 Madrid, Spain
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  • Hana N. Dawson,

    1. Division of Neurology, Duke University, Durham, North Carolina, USA
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  • Michael P. Vitek,

    1. Division of Neurology, Duke University, Durham, North Carolina, USA
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  • George Perry,

    1. Department of pathology, Case Western Reserve University, Cleveland, Ohio, USA
    2. College of Science, University of Texas at San Antonio, Texas, USA
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  • Mark A. Smith,

    1. Department of pathology, Case Western Reserve University, Cleveland, Ohio, USA
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  • Jesus Avila

    1. Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), Universidad Autonoma de Madrid, Madrid, Spain
    2. CIBERNED, Madrid, Spain
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Address correspondence and reprint requests to Jesus Avila, Facultad de Ciencias, Centro de Biología Molecular “Severo Ochoa”, Universidad Autónoma de Madrid, Campus de Cantoblanco, Madrid 28049, Spain. E-mail: javila@cbm.uam.es

Abstract

Analysis of brain microtubule protein from patients with Alzheimer’s disease showed decreased alpha tubulin levels along with increased acetylation of the alpha tubulin subunit, mainly in those microtubules from neurons containing neurofibrillary tau pathology. To determine the relationship of tau protein and increased tubulin acetylation, we studied the effect of tau on the acetylation-deacetylation of tubulin. Our results indicate that tau binds to the tubulin-deacetylase, histone deacetylase 6 (HDAC6), decreasing its activity with a consequent increase in tubulin acetylation. As expected, increased acetylation was also found in tubulin from wild-type mice compared with tubulin from mice lacking tau because of the tau-mediated inhibition of the deacetylase. In addition, we found that an excess of tau protein, as a HDAC6 inhibitor, prevents induction of autophagy by inhibiting proteasome function.

Ancillary